Purpose: Initially performed in prophylactic cases, indications for nipple-sparing mastectomy (NSM) have now expanded. However, trends and surgical outcomes stratified by NSM indication have not yet been fully examined.Methods: Demographics and outcomes for all NSMs performed from 2006 to 2017 were stratified by mastectomy indication and compared.Results: A total of 1212 NSMs were performed: 496 (40.9%) and 716 (59.1%) for therapeutic and prophylactic indications. Prophylactic NSMs were significantly associated with younger age (p=0.0007), bilateral reconstruction (p<0.0001), inframammary fold incisions (p<0.0001), and lower stage pathologic cancer stage (p=0.0128). Therapeutic NSMs were significantly associated with greater rates of prior and adjuvant chemoradiation (p<0.0001) as well as tissue expander-based reconstruction (p=0.0024). Absolute and relative post-operative NSM flap thickness as measured on magnetic resonance imaging was equivalent between the therapeutic and prophylactic groups (8.86 [69.71%] versus 8.54 [64.84%] millimeters; p=0.5822). Therapeutic NSMs experienced significantly greater rates of major (p=0.0165) and minor (p=0.0421) infection, implant loss (p=0.0098), reconstructive failure (p=0.0058), and seroma (p=0.0043). Rates of major (p=0.4461) and minor (p=0.2673) mastectomy flap necrosis as well as complete (p=0.3445) and partial (p=0.7120) nipple necrosis were equivalent. The overall rate of locoregional recurrence/occurrence per NSM was 0.5%; 1.0% in therapeutic NSMs and 0.1% in prophylactic NSMs (p<0.0001).Conclusions: Approximately 40% of NSMs are currently performed for therapeutic indications. Therapeutic NSMs had higher rates of infectious complications and reconstructive failure, although this does not appear secondary to more aggressive oncologic extirpation. Rates of locoregional cancer recurrence/occurrence is low, but occurs significantly more often after therapeutic NSM.